ABSTRACT (Overall Component) The overarching goals of our Environmental Health Sciences Center (EHSC) are to prevent disease and improve public health through innovative programs of excellence in environmental health sciences research, to engage communities to address environmental health issues, and to enhance career development of talented environmental health investigators. The EHSC provides the framework for the generation of novel research findings and their conversion into effective resources for public health officials, medical professionals, and the community. This tradition of success is based on our ability to recruit broad multi- and interdisciplinary expertise, maintain a strong emphasis on basic science principles while incorporating clinical and translational approaches, and effectively interact with the community. The specific mission of the EHSC at Rochester is to improve public health through the generation of fundamental knowledge and elaboration of mechanisms by which chemical exposures, alone or through interaction with other modifying factors, contribute to cumulative health risk across the life span. As such, the theme that guides and integrates EHSC research and community engagement programs is the understanding of interactions of environmental and occupational agents with diverse individual contexts across the lifespan in modulating human disease and dysfunction. The goals of the Center are achieved through a major focus on three research programs: Pulmonary & Cardiovascular Disease Program, Neurodevelopmental & Neurodegenerative Disease Program, and Musculoskeletal Disease Program. While the Center is structurally organized into these Disease Programs, shared thematic biological processes, including immunological responses & inflammation, stem cell biology, early life sensitivities and mechanisms of adult disease, epigenetics, and nutritional/dietary factors, weave these programs together and synergize the research. These research efforts are supported by several structural units: Administrative Core, Integrative Health Sciences Facility Core, Biostatistics Facility Core, Community Outreach & Engagement Core, Pilot Project Program, and Career Development Program for Environmental Health Science Investigators.